System and method for four dimensional angiography and fluoroscopy

ABSTRACT

A method for generating time-resolved 3D medical images of a subject by imparting temporal information from a time-series of 2D medical images into 3D images of the subject. Generally speaking, this is achieved by acquiring image data using a medical imaging system, generating a time-series of 2D images of a ROI from at least a portion of the acquired image data, reconstructing a 3D image substantially without temporal resolution from the acquired image data, and selectively combining the time series of 2D images with the 3D image. Selective combination typically involves registering frames of the time-series of 2D images with the 3D image, projecting pixel values from the 2D image frames “into” the 3D image, and weighting the 3D image with the projected pixel values for each frame of the time-series of 2D images.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Patent Application No. 61/497,392 titled SYSTEM AND METHOD FOR FOUR DIMENSIONAL ANGIOGRAPHY AND FLUOROSCOPY and filed Jun. 15, 2011, the entire contents of each of which are incorporated by reference in their entirety herein

This application is related to U.S. patent application Ser. No. 12/692,340 titled SYSTEM AND METHOD FOR FOUR DIMENSIONAL ANGIOGRAPHY AND FLUOROSCOPY filed Jan. 22, 2010, which is a continuation-in-part of U.S. patent application Ser. No. 12/542,376 titled SYSTEM AND METHOD OF TIME-RESOLVED, THREE-DIMENSIONAL ANGIOGRAPHY filed Aug. 17, 2009, the entire contents of each of which are incorporated by reference in their entirety herein.

The application is also related to PCT Application PCT/US2010/045637 titled SYSTEM AND METHOD FOR FOUR DIMENSIONAL ANGIOGRAPHY AND FLUOROSCOPY filed Aug. 16, 2010 the entire contents of which are incorporated by reference in their entirety herein.

BACKGROUND

The following description is provided to assist the understanding of the reader. None of the information provided or references cited is admitted to be prior art.

The present disclosure relates to angiography and, more particularly, to a system and method for producing time-resolved, three-dimensional (thus, resulting in four dimensional) angiographic and fluoroscopic images.

Since the introduction of angiography beginning with the direct carotid artery punctures of Moniz in 1927, there have been ongoing attempts to develop angiographic techniques that provide diagnostic images of the vasculature, while simultaneously reducing the invasiveness associated with the procedure. For decades, post-processing of images was largely limited to the use of film subtraction techniques. Initial angiographic techniques involved direct arterial punctures and the manipulation of a needle through which a contrast medium was injected. These practices were associated with a significant incidence of serious complications. The development of percutaneous techniques allowing the use of a single catheter to study multiple arterial segments reduced, but this by no means eliminated, these adverse events. In the late 1970's, a technique known as digital subtraction angiography (hereinafter, “DSA”) was developed based on real-time digital processing equipment. Because of the advantages of digital processing, it was originally hoped that DSA could be consistently implemented using an intravenous (hereinafter, “IV”) injection of contrast medium, thus reducing both the discomfort and the incidence of complications associated with direct intraarterial (hereinafter, “IA”) injections.

However, it quickly became apparent that the IV-DSA technique was limited by problems due to suboptimal viewing angles and vessel overlap that could only be reduced by repeated injections. Even then, these factors were problematic unless a projection that avoided the overlap of relevant vascular structures could be defined. Similar problems occurred when using biplane acquisitions. Also, because of the limited amount of signal associated with the IV injection of contrast medium, IV-DSA was best performed in conditions with adequate cardiac output and minimal patient motion. IV-DSA was consequently replaced by techniques that combined similar digital processing with standard IA angiographic examinations. Nevertheless, because DSA can significantly reduce both the time necessary to perform an angiographic examination and the amount of contrast medium that was required, its availability resulted in a significant reduction in the adverse events associated with angiography. Due to steady advancements in both hardware and software, DSA can now provide exquisite depictions of the vasculature in both two-dimensional (hereinafter, “2D”) and rotational three-dimensional (hereinafter, “3D”) formats. 3D-DSA has become an important component in the diagnosis and management of people with a large variety of central nervous system vascular diseases.

Current limitations in the temporal resolution capabilities of x-ray angiographic equipment require that rotational acquisitions be obtained over a minimum time of about 5 seconds. Even with perfect timing of an acquisition so that arterial structures are fully opacified at the onset of a rotation, there is almost always some filling of venous structures by the end of the rotation. Display of a “pure” image of arterial anatomy is only achieved by thresholding such that venous structures, which contain lower concentrations of contrast medium than arterial structures, are no longer apparent in the image. This limitation is a significant factor in making it prohibitively difficult to accurately measure the dimensions of both normal and abnormal vascular structures. Current DSA-based techniques do not depict the temporal sequence of filling in a reconstructed 3D-DSA volume.

In recent years competition for traditional DSA has emerged in the form of computed tomography angiography (hereinafter, “CTA”) and Magnetic Resonance Angiography (hereinafter, “MRA”). CTA provides high spatial resolution, but it is not time-resolved unless the imaging volume is severely limited. CTA is also limited as a standalone diagnostic modality by artifacts caused by bone at the skull base and the contamination of arterial images with opacified venous structures. Further, CTA provides no functionality for guiding or monitoring minimally-invasive endovascular interventions. Significant advances have been made in both the spatial and the temporal resolution qualities of MRA. Currently, gadolinium-enhanced time-resolved MRA (hereinafter, “TRICKS”) is widely viewed as a dominant clinical standard for time-resolved MRA. TRICKS enables voxel sizes of about 10 mm³ and a temporal resolution of approximately 10 seconds. Advancements such as HYBRID HYPR MRA techniques, which violate the Nyquist theorem by factors approaching 1000, can provide images with sub-millimeter isotropic resolution at frame times just under 1 second. Nonetheless, the spatial and temporal resolution of MRA are not adequate for all imaging situations and its costs are considerable.

Shortcomings of existing angiography methods are particularly prevalent when imaging the small size and convoluted course of the intracranial vasculature. With traditional DSA it is difficult or impossible to image and display these structures without the overlap of adjacent vessels. This problem is compounded when visualizing abnormal structures with complex geometry, such as aneurysms, or when abnormally fast or slow flow is present, such as in vascular malformations or ischemic strokes. As cerebrovascular diseases are increasingly treated using minimally invasive endovascular techniques, where such treatment is dependent upon imaging techniques for visualization of vascular structures, it is becoming more important to develop imaging methods that allow clear definition of vascular anatomy and flow patterns. Such information is becoming a prerequisite for both pre-treatment planning and the guidance of interventional procedures. For example, the endovascular treatment of vascular disease can require accurate navigation through the small and tortuous vessels of the brain and spinal cord. Currently this involves the use of a roadmap that must be “reset” numerous times during a typical procedure. In fact, it is not uncommon to have 15 to 20 resets during a given procedure. Not only does this use large amounts of contrast medium, but the risk of thromboembolic complications increases with each injection.

It would therefore be desirable to have a system and method for producing time-resolved, 3D images of the vasculature with an improved spatial and temporal resolution over those possible currently. The method would allow arterial vasculature to be distinguished from venous vasculature, which would in turn allow the use of IV injections of contrast medium in cases where IA injections are currently performed. This would also allow 3D volumes to be viewed as a dynamic sequence, allowing an improved understanding of vascular diseases and providing a basis for more accurate and versatile roadmaps for use in interventional procedures.

BRIEF SUMMARY

The present disclosure overcomes the aforementioned drawbacks by providing a system and method for generating a detailed series of time-resolved, 3D medical images of a subject, with both high temporal resolution and excellent spatial resolution, by imparting temporal information from either a separately acquired time-series of 2D images into a still 3D rotational DSA image or, in a preferred embodiment, using the intrinsic time information provided by the 2D projection images from which the 3D rotational DSA image is formed. In the preferred method, image data from a subject is acquired using a medical imaging system and a single contrast injection to generate a time-series of 2D images from which a 3D image, substantially without temporal resolution, is reconstructed from at least a portion of the acquired image data consisting of 2D angular projections. The method also includes producing a series of time-resolved 3 images of the subject by selectively combining the 3D image, substantially without temporal resolution, and the time-series of 2D images. This preferred method can be implemented with a system consisting of a single x-ray source and detector array. In the preferred method, the signal-to-noise ratio of each image in the time series is substantially the same as that of the single 3D image. In the preferred method, it has been discovered that pairs of projections can be separated by angles on the order of 60 degrees. In spite of this, the temporal behavior is dominated by the earlier projection whereas the second serves primarily to remove potential ambiguities that may occur in the multiplication process. Venous signals in the projection at the larger angle are zeroed since they are not present in the earlier frame. The overall time frame is generally formed as the square root of two products—the product of the first frame projection and the 3D volume, and the product of the second projection and the 3D volume.

In an embodiment, a method is provided for producing a time-resolved 3D image of a subject by acquiring time-resolved image data from a region-of-interest (hereinafter, “ROI”) in the subject in a first acquisition, performed over a time period during which a bolus of contrast agent passes through the ROI, and then generating a time-series of 2D images from image data acquired in the first acquisition. The method also includes acquiring image data from the ROI in a second acquisition, reconstructing a 3D image substantially without temporal resolution from the image data acquired in the second acquisition, and producing a time-resolved 3D image of the subject by selectively combing the time-series of 2D images and the 3D image substantially without temporal resolution. In this method, the first acquisition may be performed using either a single plane or biplane x-ray system. Once again, the method includes transferring the signal-to-noise ratio of the single 3D image to the individual time frames. This is accomplished through convolution of the projection data prior to multiplication by the 3D volume.

In another embodiment, a method is provided for producing a time-resolved 3D image of a subject by acquiring projection views of a region-of-interest (ROI) in the subject over a selected time period using a rotational acquisition, while a bolus of contrast agent passes through the ROI during a portion of the selected time period. Again, the method includes generating a time-series of 2D images of the ROI from projection views acquired during the portion of the selected time period during which the bolus of contrast agent passes through the ROI. This method also includes the reconstruction of a 3D image of the ROI, substantially without temporal resolution, from substantially all of the acquired projection views and producing the time-resolved 3D image of the subject by selectively combining the time-series of 2D images and the 3D image without temporal resolution.

The described method further includes 3D time-resolved tracking on IV devices such as catheters and coils. This process involves the use of a subtracted series of 2D projection images of the device obtained in one or, preferably, two simultaneous projections and the imbedding of this information into a 3D rotational data set so that the position of the device can be displayed from arbitrary angles without rotation of the source or detector system(s). In a preferred implementation, the various segments of the advancing device are processed from time derivative information from two simultaneous projection views. This information is multiplicatively correlated so that at any point in time the current position of the leading edge of the device is identified and can be distinguished from its previous positions. This is important in instances in which there might be coiling of a device whereby it may occupy multiple positions within the vessel lumen. The preferred method includes generating an historical path of the device which sums all previous instantaneous signals identified by the multiplicative correlation process. For application in systems having only a single source/single detector system, advancing devices not resulting in multiple instances within the lumen can be depicted using single view, time-dependent projections and displaying the device along the center line of the vessel in the orthogonal view.

Yet another embodiment includes a partial filtered back projection reconstruction employing one or more segments of angles which provide a weighting image that is multiplied into the static 3D rotational vascular data set. This provides a better approximation to the time-dependent perfusion of the intravascular tissue. For single source/single detector systems, the filtered back projection is generated with a single angular segment composed of several adjacent projections. For bi-plane systems, two segments separated by approximately 90 degrees can be employed. To remove the effects of time-dependent vascular behavior, vessels can be segmented out before multiplication of the tissue component of the projections and the tissue component of the static 3D data set.

In one aspect, a method is disclosed which includes acquiring image data from a subject using a medical imaging system, generating a time-series of two-dimensional images from at least a portion of the acquired image data, and reconstructing a three-dimensional image substantially without temporal resolution from at least a portion of the acquired image data. The method also includes producing a time-resolved three-dimensional image of the subject by selectively combining the three-dimensional image substantially without temporal resolution and the time-series of two-dimensional images.

Another aspect of the present disclosure includes a method for producing a time-resolved three-dimensional image of a subject by acquiring time-resolved image data from a region-of-interest (ROI) in the subject in a first acquisition performed over a time period during which a bolus of contrast agent passes through the ROI and generating a time-series of two-dimensional images from image data acquired in the first acquisition. The method also includes acquiring image data from the ROI in a second acquisition, reconstructing a three-dimensional image substantially without temporal resolution from the image data acquired in the second acquisition, and producing a time-resolved three-dimensional image of the subject by selectively combing the time-series of two-dimensional images and the three-dimensional image substantially without temporal resolution. In this method, the first acquisition may be performed using a single plane or biplane x-ray system.

In yet another aspect, a method is provided for producing a time-resolved three-dimensional image of a subject by acquiring projection views of a region-of-interest (ROI) in the subject over a selected time period using a rotational acquisition, while a bolus of contrast agent passes through the ROI during a portion of the selected time period. The method also includes generating a time-series of two-dimensional images of the ROI from projection views acquired during the portion of the selected time period during which the bolus of contrast agent passes through the ROI. The method further includes reconstructing a three-dimensional image of the ROI substantially without temporal resolution from substantially all of the acquired projection views and producing the time-resolved three-dimensional image of the subject by selectively combining the time-series of two-dimensional images and the three-dimensional image without temporal resolution

In one aspect, a method is disclosed for producing a time-resolved three-dimensional image of a subject, the method including: acquiring image projection data from the subject using a medical imaging system during a single contrast injection, the medical imaging system including a single source/single detector system; generating a time-series of two-dimensional images from at least a portion of the acquired image projection data; reconstructing a three-dimensional image substantially without temporal resolution from at least a portion of the acquired image projection data; and producing a time-resolved three-dimensional image having a signal-to-noise ratio substantially higher than a signal-noise-ratio of the acquired image projection data by selectively combining the three-dimensional image substantially without temporal resolution and the time-series of two-dimensional images.

In some embodiments, a subtracted vessel-only time-series of two-dimensional images is generated by subtracting at least one of a time frame of the time-series and an average of time frames of the time-series acquired before arrival of contrast from frames of the time-series acquired after an arrival of contrast during the single contrast injection.

Some embodiments include registering the reconstructed three-dimensional image substantially without temporal resolution to the subtracted vessel-only time-series of two-dimensional images; convolving the subtracted vessel-only time-series of two-dimensional images using a two-dimensional spatial kernel; projecting a value of each pixel in the subtracted vessel-only time-series of two-dimensional images along a line extending through each respective pixel in a direction perpendicular to a plane of the time-series of two-dimensional images; and multiplying the three-dimensional image substantially without temporal resolution with the projected value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images to produce the time-resolved three-dimensional image.

In some embodiments, a signal in the time-resolved three-dimensional image corresponding to undesired vascular structures in a region being imaged is zeroed by multiplication of the three-dimensional image substantially without temporal resolution with the projected value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images, which is substantially free of signals corresponding to undesired vascular structures in the region being imaged.

In some embodiments, multiplying the three-dimensional image is repeated at additional angles. In some embodiments, a final image is an nth root of a product of the multiplication at n angles.

When vessel overlap occurs in the projections it is useful to use the minimum vascular value obtained as a result of multiple angle multiplications of the projection and the 3D time-independent volume. For each multiplication, a square root is generally taken. For any voxel, the minimum value of this square root, obtained at the various projection angles used (e.g., two or more), is taken to provide the best estimate of the voxel value.

In some embodiments, the final image is derived from the minimum values resulting from image estimates obtained by multiplication at two or more angles.

In some embodiments, for each time frame, the minimum values are determined on a voxel by voxel basis. In some embodiments, for each time frame, each of the image estimates obtained by multiplication at two or more angles comprises a square root of the product of the three-dimensional image substantially without temporal resolution with a projection at a respective one of the two or more angles.

Some embodiments include calculating one or more voxel intensity curves as a function of multiple projection angles for the time resolved three dimensional image; identifying at least one anomaly in at least one voxel intensity curve; and, for the voxel corresponding to the anomaly, averaging the voxel intensity over multiple projection angles. Some embodiments include applying a spatially dependent temporal filter to the time resolved three dimensional image.

Some embodiments include determining a temporal parameter for each voxel of the time-resolved three-dimensional image, where the temporal parameter is at least one of a mean transit time and time-to-fractional peak.

In some embodiments, determining a temporal parameter includes removing shadowing artifacts from the time-resolved three-dimensional image based on the temporal parameter.

In some embodiments, determining a temporal parameter includes superimposing a color coded display of the temporal parameter on at least one of the time-resolved three-dimensional image and a blood volume image generated from the three-dimensional image substantially without temporal resolution.

In some embodiments, the image projection data are acquired at a fixed position of a source detector gantry of the single source/single detector system until injected contrast is detected in a field of view and generates adequate arterial and venous contrast to permit acquisition of a three-dimensional rotational data set with substantially uniform contrast throughout whereby rotation of the source detector gantry is initiated.

In some embodiments, additional time-resolved outflow projection data are acquired at a final angle of the three-dimensional rotational data set acquisition and are used to produce three-dimensional time resolved outflow volumes.

In some embodiments, the single contrast injection is one of an intra-arterial injection and an intra-venous injection.

In one aspect, a method is disclosed for producing a time-resolved three-dimensional image of a subject, the method including: acquiring image projection data from the subject using a medical imaging system during multiple contrast injections acquired at multiple source-detector orientations, the medical imaging system including a single source/single detector array; and generating a subtracted vessel-only time-series of two-dimensional images from the acquired image projection data at the multiple source-detector orientations.

In some embodiments, the image projection data is acquired at multiple rotation angles during one of the multiple contrast injections.

In some embodiments, a three-dimensional image substantially without temporal resolution is reconstructed from at least a portion of the acquired image projection data.

Some embodiments include producing a time-resolved three-dimensional image with a signal-to-noise ratio substantially higher than a signal-to-noise ratio of the acquired image projection data by selectively combining the three-dimensional image substantially without temporal resolution and the subtracted vessel-only time-series of two-dimensional images.

In some embodiments, a signal in the time-resolved three-dimensional image corresponding to undesired vascular structures in a region being imaged is zeroed by multiplication of the three-dimensional image substantially without temporal resolution with the projected value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images, which is substantially free of signals corresponding to undesired vascular structures in the region being imaged.

In some embodiments, multiplying the three-dimensional image is repeated at additional angles. In some embodiments, a final image is an nth root of a product of the multiplication at n angles.

When vessel overlap occurs in the projections it is useful to use the minimum vascular value obtained as a result of multiple angle multiplications of the projection and the 3D time-independent volume. For each multiplication, a square root is generally taken. For any voxel, the minimum value of this square root, obtained at the various projection angles used (e.g., two or more), is taken to provide the best estimate of the voxel value.

In some embodiments, a final image is derived from the minimum values resulting from image estimates obtained by multiplication at two or more angles.

In some embodiments, for each time frame, the minimum values are determined on a voxel by voxel basis. In some embodiments, for each time frame, each of the image estimates obtained by multiplication at two or more angles comprises a square root of the product of the three-dimensional image substantially without temporal resolution with a projection at a respective one of the two or more angles.

Some embodiments include calculating one or more voxel intensity curves as a function of multiple projection angles for the time resolved three dimensional image; identifying at least one anomaly in at least one voxel intensity curve; and for the voxel corresponding to the anomaly, averaging the voxel intensity over multiple projection angles. Some embodiments include applying a spatially dependent temporal filter to the time resolved three dimensional image.

Some embodiments include determining a temporal parameter for each voxel of the time-resolved three-dimensional image, where the temporal parameter is at least one of a mean transit time and time-to-fractional peak. In some embodiments, determining a temporal parameter includes removing shadowing artifacts from the time-resolved three-dimensional image based on the temporal parameter. In some embodiments, determining a temporal parameter includes superimposing a color coded display of the temporal parameter on at least one of the time-resolved three-dimensional image and a blood volume image generated from the three-dimensional image substantially without temporal resolution.

In some embodiments, the multiple contrast injections are one of intra-arterial injections and intra-venous injections.

In one aspect, a method is disclosed for producing a time-resolved three-dimensional image of a subject, the method including: acquiring image projection data from the subject using a medical imaging system during a single contrast injection, the medical imaging system including a bi-plane system having two separate source detector systems; generating a subtracted vessel-only time-series of two-dimensional images from at least a portion of the acquired image projection data from each of the source detector systems obtained at multiple angles; reconstructing a three-dimensional image substantially without temporal resolution from at least a portion of the acquired image projection data; and producing a time-resolved three-dimensional image having a signal-to-noise ratio substantially higher than a signal-to-noise ratio of the acquired image projection data by selectively combining the three-dimensional image substantially without temporal resolution and the subtracted vessel-only time-series of two-dimensional images.

Some embodiments include: registering the reconstructed three-dimensional image substantially without temporal resolution to the subtracted vessel-only time-series of two-dimensional images obtained at multiple angles; convolving the subtracted vessel-only time series of two-dimensional images using a two-dimensional spatial kernel; projecting a value of each pixel in the subtracted vessel-only time-series of two-dimensional images along a line extending through each respective pixel in a direction perpendicular to a plane of the subtracted vessel-only time-series of two-dimensional images; and multiplying the three-dimensional image substantially without temporal resolution with the value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images to produce the time-resolved three-dimensional image.

In some embodiments, a signal in the time-resolved three-dimensional image corresponding to undesired vascular structures in a region being imaged is zeroed by multiplication of the three-dimensional image substantially without temporal resolution with the projected value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images, which is substantially free of signals corresponding to undesired vascular structures in the region being imaged.

In some embodiments, a final image is an nth root of a product of the multiplication at n angles.

When vessel overlap occurs in the projections it is useful to use the minimum vascular value obtained as a result of multiple angle multiplications of the projection and the 3D time-independent volume. For each multiplication, a square root is generally taken. For any voxel, the minimum value of this square root, obtained at the various projection angles used (e.g., two or more), is taken to provide the best estimate of the voxel value.

In some embodiments, the final image is derived from the minimum values resulting from image estimates obtained by multiplication at two or more angles.

In some embodiments, for each time frame, the minimum values are determined on a voxel by voxel basis. In some embodiments, for each time frame, each of the image estimates obtained by multiplication at two or more angles comprises a square root of the product of the three-dimensional image substantially without temporal resolution with a projection at a respective one of the two or more angles.

Some embodiments include calculating one or more voxel intensity curves as a function of multiple projection angles for the time resolved three dimensional image; identifying at least one anomaly in at least one voxel intensity curve; and for the voxel corresponding to the anomaly, averaging the voxel intensity over multiple projection angles. Some embodiments include applying a spatially dependent temporal filter to the time resolved three dimensional image.

Some embodiments include determining a temporal parameter for each voxel of the time-resolved three-dimensional image, where the temporal parameter is at least one of a mean transit time and time-to-fractional peak.

In some embodiments, determining a temporal parameter includes removing shadowing artifacts from the time-resolved three-dimensional image based on the temporal parameter.

In some embodiments, determining a temporal parameter includes superimposing a color coded display of the temporal parameter on at least one of the time-resolved three-dimensional image and a blood volume image generated from the three-dimensional image substantially without temporal resolution.

In some embodiments, the image projection data are acquired at fixed positions of two source detector gantries of the respective two source detector systems until injected contrast is detected in a field of view and generates adequate arterial and venous contrast to permit acquisition of a 3D rotational data set with substantially uniform contrast throughout whereby rotation of at least one of the two source detector gantries is initiated.

In some embodiments, additional time-resolved outflow projection data are acquired at a final angle of the three-dimensional rotational data set acquisition and are used to produce three-dimensional time resolved outflow volumes.

In one aspect, a method is disclosed for producing a time-resolved three-dimensional image of a subject, the method including: acquiring first image projection data from the subject using a medical imaging system during a first contrast injection, the medical imaging system including a bi-plane system having two separate source detector systems; generating a subtracted vessel-only time-series of two-dimensional images from at least a portion of the acquired first image projection data from each of the source detector systems; acquiring second image projection data from the subject using the medical imaging system during a second contrast injection; reconstructing a three-dimensional image substantially without temporal resolution from at least a portion of the acquired second image projection data; and producing a time-resolved three-dimensional image having a signal-to-noise ratio substantially higher than a signal-to-noise ratio of the acquired first image projection data by selectively combining the three-dimensional image substantially without temporal resolution and the subtracted vessel-only time-series of two-dimensional images.

In one aspect, a method is disclosed for producing time-resolved three-dimensional vascular data set images of a subject, the method including: acquiring partial angle filtered-back image projection data from the subject using a medical imaging system during at least one of a single contrast injection and multiple contrast injections; generating a progressive time-series of two-dimensional images from at least a portion of the acquired image projection data over an advancing limited angular range; reconstructing a three-dimensional image substantially without temporal resolution from at least a portion of the acquired image projection data; and producing a time-resolved three-dimensional image having a signal-to-noise ratio substantially higher than a signal-to-noise ratio of the acquired image projection data by selectively combining the three-dimensional image substantially without temporal resolution and the progressive time-series of two-dimensional images, where the progressive time-series of two-dimensional images is used to weight and multiply the three-dimensional image substantially without temporal resolution to produce the time-resolved three-dimensional image.

Some embodiments include applying a threshold elimination signal prior to the progressive time-series of two-dimensional images being used to weight and multiply the three-dimensional image substantially without temporal resolution to remove vascular information.

In one aspect a method is disclosed for producing, on a single-plane fluoroscopic system, time-resolved, three-dimensional fluoroscopic images of an interventional device superimposed on a three-dimensional vascular roadmap provided by a four-dimensional DSA time frame, the method including: selecting a four-dimensional DSA time frame for a vascular roadmap; generating a subtracted time-series of fluoroscopic images of the interventional device obtained at a single source-detector gantry angle; combining the subtracted time-series of fluoroscopic images into a three-dimensional vascular space by multiplying the subtracted time-series of fluoroscopic images by the three-dimensional vascular roadmap; and displaying ongoing subtracted time-series of fluoroscopic images superimposed on the three-dimensional vascular roadmap from arbitrary directions by forming maximum intensity projections through the combined fluoroscopic images and three-dimensional vascular roadmap. In some embodiments, a position of the interventional device in a direction of multiplying rays is substantially in a center of a vessel of a subject under examination.

In one aspect, a method is disclosed for producing a time-resolved three-dimensional image of a subject, the method including the steps of: a) acquiring image data from the subject using a medical imaging system; b) generating a time-series of two-dimensional images from at least a portion of the acquired image data; c) reconstructing a three-dimensional image substantially without temporal resolution from at least a portion of the acquired image data; and d) producing a time-resolved three-dimensional image of the subject by selectively combining the three-dimensional image substantially without temporal resolution and the time-series of two-dimensional images.

Some embodiments include the steps: d) i) registering the reconstructed three-dimensional image substantially without temporal resolution to the time-series of two-dimensional images; d) ii) projecting a value of each pixel in the time-series of two-dimensional images along a line extending through each respective pixel in a direction perpendicular to a plane of the time-series of two-dimensional images; and d) iii) multiplying the three-dimensional image substantially without temporal resolution with the value of each pixel projected in step d) ii) for each time frame of the time-series of two-dimensional images to produce the time-resolved three-dimensional image.

In some embodiments, signal in the time-resolved three-dimensional image corresponding to undesired vascular structures in a region being imaged is zeroed by multiplication of the three-dimensional image substantially without temporal resolution with the values projected from the time-series of two-dimensional images, which is substantially free of signal corresponding to the undesired vascular structures in the region being imaged.

Some embodiments include the step e) determining temporal parameter for each voxel of the time-resolved three-dimensional image, where the temporal parameter is at least one of a mean transit time (MTT) and time-to-fractional-peak. In some embodiments, step e) further includes removing shadowing artifacts from the time-resolved three-dimensional image based on the temporal parameter.

In some embodiments, step e) includes superimposing a color coded display of the temporal parameter on at least one of the time-resolved three-dimensional image and a blood volume image generated from the three-dimensional image substantially without temporal resolution.

Some embodiments include the steps a) i) acquiring image data from a selected vascular region of the subject at a first angle and at a second angle substantially orthogonal to the first angle using an x-ray system; b) i) generating a first and second time-series of two-dimensional images from the image data acquired at the first and second angles, respectively, so that the first and second time-series of two-dimensional images are substantially orthogonal and are substantially free of signals corresponding to non-vascular structures; d) i) registering the reconstructed three-dimensional image substantially without temporal resolution to the first and second time-series of two-dimensional images; d) ii) projecting a value of each pixel in the first time-series of two-dimensional images along an axis perpendicular to that of the first time-series of two-dimensional images and projecting a value of each pixel in the second time-series of two-dimensional images along an axis perpendicular to that of the second time-series of two-dimensional images; and d) iii) multiplying the three-dimensional image substantially without temporal resolution with the value of each pixel projected in step d) ii) for each time frame of the time-series of two-dimensional images to produce the time-resolved three-dimensional image.

Some embodiments include the steps: a) ii) acquiring three-dimensional image data from the selected vascular region using a rotational x-ray system; and c) i) reconstructing the three-dimensional image substantially without temporal resolution in which the selected vascular region is substantially opacified from the acquired three-dimensional image data and where the reconstructed three-dimensional image substantially without temporal resolution is substantially free of signal corresponding to non-vascular structures.

In some embodiments, the image data acquired in step a) i) is acquired over a time period during which a first contrast agent bolus passes through the selected vascular region and the image data acquired in step a) ii) is acquired following passage of a second contrast agent bolus through the selected vascular region.

In some embodiments, signal corresponding to non-vascular structures is removed from the image generated in step b) ii) by subtracting image data acquired prior to the passage of the first contrast agent through the selected vascular region from the image data acquired in step a) i).

In some embodiments, the signal corresponding to non-vascular structures is removed from the image reconstructed in step c) i) by subtracting image data acquired prior to the passage of the second contrast agent bolus through the subject of interest from the image data acquired in step a) ii).

In some embodiments, the first and second contrast agents are administered using at least one of an intravenous injection and an intra-arterial injection.

Some embodiments include steps: a) i) acquiring projection views of a region-of-interest (ROI) in the subject over a selected time period using a rotational x-ray system, where a bolus of contrast agent passes through the ROI during a portion of the selected time period; b) i) generating a time-series of two-dimensional images from projection views acquired during the portion of the selected time period during which the bolus of contrast agent passed through the ROI; and c) i) reconstructing a three-dimensional image substantially without temporal resolution from substantially all of the acquired projection views.

In some embodiments, the contrast agent is administered using an intravenous injection and signal corresponding to non-vascular structures is removed from images generated in step b) i) and reconstructed in step c) i) by subtracting image data acquired from the ROI prior to passage of the contrast agent bolus through the ROI.

Some embodiments include the step e) generating a roadmap for an interventional procedure based on the time-resolved three-dimensional image of the subject. In some embodiments, step e) further includes embedding real-time surgical device information within at least one selected time frame of the time-resolved three-dimensional image of the subject. In some embodiments, step e) further includes embedding surgical device information acquired at a first and second angle using a biplane fluoroscopy system within corresponding angles of the time-resolved three-dimensional image of the subject. In some embodiments, step e) further includes: embedding surgical device information acquired at a first angle using a single-plane fluoroscopy system within a corresponding angle of the time-resolved three-dimensional image to produce a hybrid data set, where along a second angle orthogonal to the first angle surgical device information is embedded within a center of vessels depicted in the time-resolved three-dimensional image; and superimposing a maximum intensity projection (MIP) through the hybrid data set on a MIP though the time-resolved three-dimensional image subject at a corresponding angle.

In some embodiments, the surgical device is at least one of a catheter, coil, stent, and guide wire.

In some embodiments, step e) further includes superimposing a real-time single-plane fluoroscopy image containing the surgical device information and acquired at the selected angle on a MIP through the time-resolved three-dimensional image of the subject at the corresponding angle.

In some embodiments, step d) further includes taking a root of the time-resolved three-dimensional image to compensate for increases in image intensity caused by selectively combining the three-dimensional image substantially without temporal resolution and the time-series of two-dimensional images.

In one aspect, a method is disclosed for producing a time-resolved three-dimensional image of a subject, the method including the steps of: acquiring time-resolved image data from a region-of-interest (ROI) in the subject in a first acquisition performed over a time period during which a bolus of contrast agent passes through the ROI; generating a time-series of two-dimensional images from image data acquired in the first acquisition; acquiring image data from the ROI in a second acquisition; reconstructing a three-dimensional image substantially without temporal resolution from the image data acquired in the second acquisition; and producing a time-resolved three-dimensional image of the subject by selectively combing the time-series of two-dimensional images and the three-dimensional image substantially without temporal resolution.

In some embodiments, producing the time-resolved three-dimensional image of the subject includes: registering the reconstructed three-dimensional image substantially without temporal resolution to the time-series of two-dimensional images; projecting a value of each pixel in the time-series of two-dimensional images along a line extending through each respective pixel in a direction perpendicular to a plane of the time-series of two-dimensional images; and multiplying the three-dimensional image substantially without temporal resolution with the value projected for each pixel for each time frame of the time-series of two-dimensional images to produce the time-resolved three-dimensional image.

In some embodiments, signal in the time-resolved three-dimensional image corresponding to undesired structures in the ROI is zeroed by a multiplication of the three-dimensional image substantially without temporal resolution with the value projected for each pixel from the time-series of two-dimensional images, which is substantially free of signal corresponding to the undesired structures in the ROI.

In some embodiments, acquiring image data in the first acquisition includes acquiring time-resolved two-dimensional image data at a first angle and an orthogonal second angle using a biplane fluoroscopy system; generating the time-series of two-dimensional images includes reconstructing a first and second time-series of two-dimensional images from the image data acquired at the first and second angles, respectively; and producing the time-resolved three-dimensional image includes: registering the reconstructed three-dimensional image substantially without temporal resolution to the first and second time-series of two-dimensional images; projecting a value of each pixel in the first and second time-series of two-dimensional images along a line extending through each respective pixel in a direction perpendicular to each respective plane of the first and second time-series of two-dimensional images; and multiplying the three-dimensional image substantially without temporal resolution with the value projected for each pixel for each time frame of the first and second time-series of two-dimensional images to produce the time-resolved three-dimensional image.

In some embodiments, acquiring the image data in the second acquisition is performed using a rotational x-ray system following an administration of a contrast agent using at least one of intravenous injection and intra-arterial injection.

In some embodiments, the contrast agent that passes through the ROI in the first acquisition is administered using at least one of an intravenous injection and an intra-arterial injection.

In some embodiments, signal corresponding to non-vascular structures in the time-series of two-dimensional images and the three-dimensional image substantially without temporal resolution is removed by subtracting image data acquired from the ROI prior to passage of contrast agent from the image data acquired in the first and second acquisitions.

Some embodiments include the step of generating a roadmap for an interventional procedure based on the time-resolved three-dimensional image of the subject.

In some embodiments, generating the roadmap further includes embedding real-time surgical device information within at least one selected time frame of the time-resolved three-dimensional image of the subject.

In one aspect, a method is disclosed for producing a time-resolved three-dimensional image of a subject, the method including the steps of: acquiring projection views of a region-of-interest (ROI) in the subject over a selected time period using a rotational acquisition, where a bolus of contrast agent passes through the ROI during a portion of the selected time period; generating a time-series of two-dimensional images of the ROI from projection views acquired during the portion of the selected time period during which the bolus of contrast agent passes through the ROI; reconstructing a three-dimensional image of the ROI substantially without temporal resolution from substantially all of the acquired projection views; and producing the time-resolved three-dimensional image of the subject by selectively combining the time-series of two-dimensional images and the three-dimensional image without temporal resolution.

In some embodiments, producing the time-resolved three-dimensional image of the subject includes: registering the reconstructed three-dimensional image substantially without temporal resolution to the time-series of two-dimensional images; projecting a value of each pixel in the time-series of two-dimensional images along a line extending through each respective pixel in a direction perpendicular to a plane of the time-series of two-dimensional images; and multiplying the three-dimensional image substantially without temporal resolution with the values projected for each pixel for each time frame of the time-series of two-dimensional image to produce the time-resolved three-dimensional image.

In some embodiments, signal in the time-resolved three-dimensional image corresponding to undesired structures in the ROI is zeroed by multiplication of the three-dimensional image without temporal resolution with the time-series of two-dimensional images, which is substantially free of signal corresponding to the undesired vascular structures.

In some embodiments, signal corresponding to non-vascular structures is removed from the time-series of two-dimensional images and the three-dimensional image substantially without temporal resolution by subtracting image data acquired from the ROI prior to passage of the contrast agent bolus through the ROI from the acquired projection views.

In some embodiments, the projection views acquired during the portion of the selected time period during which the bolus of contrast agent passes through the ROI are acquired over a limited angular range of the rotational acquisition.

In some embodiments, each frame of the time-resolved two-series of images of the ROI corresponds to a given angle within the limited angular range and producing the time-resolved three-dimensional image of the subject includes: registering each time frame of the time-series of two-dimensional images to the reconstructed three-dimensional image substantially without temporal resolution at a corresponding angle; projecting a value of each pixel in the time-series of two-dimensional images along a line extending through each respective pixel in a direction perpendicular to a plane of each respective time frame of the time-resolved two-dimensional image; and multiplying the three-dimensional image substantially without temporal resolution with the value projected for each pixel for each time frame of the time-series of two-dimensional images to produce the time-resolved three-dimensional image.

In some embodiments, the contrast agent is administered to the subject using at least one of an intravenous injection and an intra-arterial injection.

Some embodiments include the step of generating a roadmap for an interventional procedure based on the time-resolved three-dimensional image of the subject.

In some embodiments, generating the roadmap further includes embedding surgical device catheter information within at least one selected time frame of the time-resolved three-dimensional image of the subject.

Various embodiments may include any of the aspects, features, elements, steps, etc., described above either alone, or in any suitable combination

Additional features and advantages of the present disclosure are described in, and will be apparent from, the following Detailed Description and the Drawing.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

FIGS. 1A and 1B depict a rotational x-ray system configured to carry out a process in accordance with the present disclosure;

FIG. 2 is a flowchart setting forth the general steps for producing a time-resolved 3D image in accordance with the present disclosure;

FIG. 3 is a flowchart setting forth the steps for producing a 4D-DSA image from the time-resolved 2D projection images acquired to produce a non-time-resolved 3D volume using a single plane x-ray system in accordance with the present disclosure;

FIG. 4 shows the timing of the injected contrast arrival relative to the initiation of the rotation of the C-arm system in accordance with the present disclosure;

FIG. 5 schematically depicts the selective combination of a 3D image with a 2D-DSA image frame acquired using a single plane x-ray system in accordance with the present disclosure;

FIG. 6 is a flowchart setting forth the steps for producing a 4D-DSA image from a pair of time-resolved 2D images acquired using temporally and angularly separated intrinsic projections in accordance with the present disclosure;

FIG. 7 is a flowchart setting forth the steps for the selective combination of a 3D image with two orthogonal 2D-DSA image frames acquired using a biplane x-ray system in accordance with the present disclosure;

FIG. 8 schematically depicts the selective combination of a 3D image reconstructed from a full set of projection views with images generated from a pair of individual projection views selected from the set in accordance with the present disclosure;

FIG. 9 schematically depicts the multiplication process involving the combination of 2D projection information from two orthogonal angles as produced from a bi-plane system and the 3D DSA volume;

FIG. 10 depicts the combination of images involved in generating a 4D fluoroscopic image, the images being temporally differentiated and used to form correlated segments of the advancing interventional device as in FIG. 11;

FIG. 11 shows the fluoroscopic images generated in accordance with FIG. 10 which are temporally subtracted with a time separation of at least one frame to generate time segments indicating the most recent change in the device tip, whereby after multiplication of these segments into the 3D volume from two projection angles the correlated segments are summed to produce a device path.

FIG. 12 shows a schematic and flow chart depicting the limited angle filtered back projection method whereby either one or two angular sectors are acquired depending on whether a single plane or bi-plane system is used; and

FIG. 13 shows a schematic and flow chart depicting the selective elimination of vascular information in the limited angle reconstruction prior to multiplication which increases sensitivity to the tissue perfusion and reduces reconstruction errors from the more dominant vascular signals.

FIG. 14 shows a schematic illustration of a vessel shadowing artifact caused by two blood vessels.

FIG. 15A shows a schematic illustration of a vessel self shadowing artifact caused by as single blood vessel.

FIG. 15B shows plot of voxel intensity vs. projection angle featuring an anomaly corresponding the vessel self shadowing artifact illustrated in FIG. 15A.

DETAILED DESCRIPTION

Referring to FIG. 1A, the present disclosure may employ a rotational x-ray system that is designed specifically for use in connection with interventional procedures. It is characterized by a gantry having a C-arm 10 which carries an x-ray source assembly 12 on one of its ends and an x-ray detector array assembly 14 at its other end. The gantry enables the x-ray source 12 and detector 14 to be oriented in different positions and angles around a patient disposed on a table 16, while enabling a physician access to the patient.

The gantry includes an L-shaped pedestal 18 which has a horizontal leg 20 that extends beneath the table 16 and a vertical leg 22 that extends upward at the end of the horizontal leg 20 that is spaced from of the table 16. A support arm 24 is rotatably fastened to the upper end of vertical leg 22 for rotation about a horizontal pivot axis 26.

The pivot axis 26 is aligned with the centerline of the table 16, and the arm 24 extends radially outward from the pivot axis 26 to support a C-arm drive assembly 27 on its outer end. The C-arm 10 is slidably fastened to the drive assembly 27 and is coupled to a drive motor (not shown) which slides the C-arm 10 to revolve it about a C-axis 28 as indicated by arrows 30. The pivot axis 26 and C-axis 28 intersect each other, at an isocenter 36 located above the table 16, and are perpendicular to each other.

The x-ray source assembly 12 is mounted to one end of the C-arm 10 and the detector array assembly 14 is mounted to its other end. The x-ray source 12 emits a beam of x-rays which are directed at the detector array 14. Both assemblies 12 and 14 extend radially inward to the pivot axis 26 such that the center ray of this beam passes through the system isocenter 36. The center ray of the beam thus can be rotated about the system isocenter around either the pivot axis 26 or the C-axis 28, or both, during the acquisition of x-ray attenuation data from a subject placed on the table 16.

The x-ray source assembly 12 contains an x-ray source which emits a beam of x-rays when energized. The center ray passes through the system isocenter 36 and impinges on a two-dimensional flat panel digital detector housed in the detector assembly 14. The detector 38 is a 2048 by 2048 element two-dimensional array of detector elements having a size of 41 cm by 41 cm. Each element produces an electrical signal that represents the intensity of an impinging x-ray and hence the attenuation of the x-ray as it passes through the patient. During a scan, the x-ray source assembly 12 and detector array assembly 14 are rotated about the system isocenter 36 to acquire x-ray attenuation projection data from different angles. The detector array is able to acquire 30 projections, or views, per second which is the limiting factor that determines how many views can be acquired for a prescribed scan path and speed.

Referring to FIG. 1B, the rotation of the assemblies 12 and 14 and the operation of the x-ray source are governed by a control mechanism 40 of the x-ray system. The control mechanism 40 includes an x-ray controller 42 that provides power and timing signals to the x-ray source 32. A data acquisition system (DAS) 44 in the control mechanism 40 samples data from detector elements 38 and passes the data to an image reconstructor 45. The image reconstructor 45 receives digitized x-ray data from the DAS 44 and performs high speed image reconstruction according to the methods of the present disclosure. The reconstructed image is applied as an input to a computer 46 which stores the image in a mass storage device 49 or processes the image further to produce parametric images according to the teachings of the present disclosure. It is contemplated that the computer 46 may be, or include components of, a digital vascular image processor (DVIP) system.

The control mechanism 40 also includes gantry motor controller 47 and a C-axis motor controller 48. In response to motion commands from the computer 46, the motor controllers 47 and 48 provide power to motors in the x-ray system that produce the rotations about respective pivot axis 26 and C-axis 28. As will be discussed below, a program executed by the computer 46 generates motion commands to the motor drives 47 and 48 to move the assemblies 12 and 14 in a prescribed scan path.

The computer 46 also receives commands and scanning parameters from an operator via console 50 that has a keyboard and other manually operable controls. An associated cathode ray tube display 52 allows the operator to observe the reconstructed image and other data from the computer 46. The operator supplied commands are used by the computer 46 under the direction of stored programs to provide control signals and information to the DAS 44, the x-ray controller 42 and the motor controllers 47 and 48. In addition, computer 46 operates a table motor controller 54 which controls the motorized table 16 to position the patient with respect to the system isocenter 36.

Whereas conventional reconstruction methods generally necessitate the acquisition of a minimum number of projections dictated by the Nyquist theorem, the present disclosure provides a fundamentally new method for imparting temporal resolution from a time-series of 2D images into 3D image volumes to create time-resolved 3D medical images. This allows, among other things, the production of 3D angiograms with both exquisite detail and high temporal resolution. The method can be implemented using a wide-variety of medical imaging systems, such as CT systems, fluoroscopy systems, and the above-discussed rotational x-ray system, either alone or in combination. Accordingly, the present description first presents a generalized method for producing time-resolved 3D images before proceeding to more specific implementations and extensions of the method.

Referring now to FIG. 2, a general method for producing a time-resolved 3D image begins at process block 100 with the acquisition of image data from a region-of-interest (ROI) in a subject using a medical imaging system, such as a CT system or a single-plane, biplane, or rotational x-ray systems. At process block 102, a time-series of 2D images is generated from at least a portion of the acquired image data. While the time-series of 2D images can have a high temporal and spatial resolution and may include images acquired at different angles around the subject, they generally cannot provide a sophisticated 3D depiction of the subject. The production of the time-series of 2D images may be convolved with a convolution kernel in order to provide local spatial coverage with a desired weighting. For example, these weighted images can provide information detailing how much of a vessel tree is present at a given time. It is contemplated that this process can increase SNR by a factor of three over that provided by the original time series pixels when using a 3×3 convolution kernel. At process block 104, a 3D image of the subject is reconstructed from the acquired image data. Though individual projections used to reconstruct this 3D image may themselves convey some degree of temporal information, the reconstructed 3D image itself is substantially free of temporal resolution. For brevity, the 3D image, substantially without temporal resolution, and the time-series of 2D images may simply be referred to as the “3D image” and “2D images,” respectively. It should be noted that the acquisition and reconstruction of the above sets of image data can be performed in accordance with constrained reconstruction techniques, such as highly constrained backprojection reconstruction (HYPR), to improve SNR and permit potential radiation and contrast agent dose reductions.

At process block 106, the time-series of 2D images and the static 3D image are selectively combined so that the temporal information included in the 2D images is imparted into the 3D image. This results in the production of a time-resolved 3D image of the subject with high temporal and spatial resolution. While the selective combination process varies based on the medical imaging system used and the nature of the acquired image data, it generally involves the steps of (1) registering the 2D images to the 3D image, (2) projecting the attenuation value of the pixels in the 2D images into the 3D image, and (3) weighting the 3D image with the projected values for each individual frame of the time-series of 2D images. It is contemplated that the temporal weighting in step (3) generally involves multiplying the projected pixel values with the 3D image. These three steps, which can be referred to as “multiplicative projection processing” (MPP), may be accompanied by additional steps to improve image quality or reduce the prevalence of errors and artifacts. For example, the intensity values of pixels and voxels in the 2D images and 3D image produced at process blocks 102 and 104 may quantify an x-ray attenuation level at a given location in the subject. These attenuation levels may not be preserved when multiplying the 3D image with projected pixel values. Accordingly, more accurate indications of the attenuation levels may be restored by taking a root of the intensity value at each voxel in the time-resolved 3D image; for example, by taking the n-th root if (n−1) different sets of 2D images are used to weight the 3D image. Other processing steps can be performed before the time-resolved 3D image is displayed at process block 108. The 2D images and 3D image produced at process blocks 102 and 104, respectively, can be produced using DSA techniques. That is, 2D images depicting the subject's vasculature can be produced by reconstructing image data acquired as a bolus of contrast passes through the ROI and subtracting out a pre-contrast, or “mask,” image acquired before the administration of contrast agent. Likewise, a 3D image of the same vasculature can be produced by reconstructing image data acquired as contrast agent occupies the ROI and subtracting out a mask image to remove signals associated with non-vascular structures. As will be discussed below, depending on the imaging situation, the time series of 2D-DSA images and the 3D-DSA images can be produced from image data acquired using a single medical imaging system and contrast agent injection or from different sets of image data acquired separately using different medical imaging systems and contrast agent injections. In either case, the time-resolved 3D image produced by combining the DSA images depicts the subject's vasculature with both excellent spatial and excellent temporal resolution and thus may be referred to as a 4D-DSA image. In addition, the 4D-DSA images can be displayed as “pure” arterial, pure venous, or composite arterial and venous images and can be fully rotated during each state of the filling of the vasculature, thereby enabling greatly simplified interpretation of vascular dynamics. The spatial resolution of these 4D-DSA images is generally on the order of 512³ pixels at about 30 frames per second. This represents an increase over traditional 3D-DSA frame rates by a factor of between 150 and 600, without any significant image quality penalty being incurred.

The acquisition of contrast enhanced image data can be performed following the administration of contrast agent to the subject via either IV or IA injection. When scanning a local area, IA injections allow high image quality and temporal resolution as well as reduced contrast agent dose. However, IV injections are often more suitable for scanning larger regions where multiple IA injections at different locations and different arteries would otherwise be required. For example, there are many clinical cases where multiple 3D-DSA acquisitions, each using a different IA injection, are performed to produce separate studies that can be merged into a larger high quality vascular tree. While separate IA acquisitions may be employed for generating the time-series of 2D images used by the present disclosure for temporal weighting, the use of an IV injection for this purpose provides a mechanism for simultaneously synchronizing imparting temporal information to all of the previously acquired anatomical locations present in instances when there are multiple, separate, IA 3D-DSA studies. This process reduces the likelihood of complications associated with IA contrast agent injections and improves scan efficiency. Further, there is the filling of arteries and veins with the same concentration of contrast medium in scans performed using IV rather than IA contrast agent injections, thus allowing the visualization of venous and arterial structures at the same threshold.

FIG. 3 shows the acquisition method that permits the complete time dependence and 3D-DSA or CTA information to be recorded with a single injection. At process block 110 the gantry angle is fixed and 2D fluoroscopic images are taken until the arrival of contrast is observed as indicated at process block 112 and the opacification of vessels is sufficiently uniform to permit the acquisition of the rotational data set as indicated at process block 114. Following the acquisition of the rotational data, the gantry angle is held fixed and additional projections are acquired until the contrast has washed out of the vessels as indicated at process block 116. The 3D volume is then reconstructed as indicated at process block 118. The projection data are 2D-DSA images that are formed by subtracting post-contrast from pre-contrast projections at each angle. These are free from non-vascular signals. The subtracted projections are convolved and multiplied into the 3D data set to form a 4D-DSA time frame as indicated at process block 120 which is immediately displayed at a preselected projection angle using a maximum intensity projection (MIP) algorithm as indicated at process block 122. At decision block 124, if some of the frames have yet to be processed, the process moves to the next frame of the time-series of 2D-DSA images at process block 125 and repeats the selective combination process 120. This cycle continues until, at decision block 124, it is determined that a 4D-DSA image has been generated for all relevant time frames.

FIG. 4 illustrates the timing of the data acquisition. Following contrast injection, the arterial vessel opacification is detected in region 126 and projection images are acquired at a fixed gantry angle. When the vessel opacification has become sufficiently uniform to support a rotational DSA acquisition the gantry angle is swept and projections are acquired over a typical angular range of 200 degrees in region 128. When the gantry sweep has been completed, additional projections are acquired to depict the washout of the contrast in region 129. All acquired 2D projection data are used to produce ongoing 4D-DSA time frame volumes.

Referring now to both FIGS. 3 and 5, the images produced thus far now can be selectively combined with the steps indicated generally at 118-120 to produce a 4D-DSA image with the detailed 3D resolution of the 3D-DSA image and the temporal resolution of the time-series 2D-DSA images. In the exemplary depiction of the selective combination process provided in FIG. 5, a single frame of the time-series of 2D-DSA images 130 includes two image regions having arterial signal 132, while the 3D-DSA image 134 includes both arterial signal 136 and venous signals 138 and 139. At process block 120, a frame of the 2D-DSA image is registered to the 3D-DSA image at the selected angle and the values of the pixels in the 2D-DSA frame are projected along a line passing through each respective pixel in a direction perpendicular to the plane of the 2D-DSA frame. The projection of pixels with arterial signal 132 into the 3D-DSA image is indicated generally at 140. For simplicity, the projection of pixels in the 2D-DSA frame with no contrast is not shown. At process block 120, the 3D-DSA image 118 is weighted by the values projected from the 2D-DSA frame to produce the 4D-DSA image 122. Typically, this includes multiplying the projected values with the voxels of the 3D image that they intersect. The weighting process results in the preservation of the arterial signal 136 and the exclusion, or “zeroing-out,” of undesired venous signal 139 in the 4D-DSA image 142. In addition, the intensity value of the arterial signal 132 in the 2D-DSA frame is imparted into the 3D arterial signal volume 136, thereby allowing the changes in arterial signal over time captured by the 2D-DSA images to be characterized in the 4D-DSA image 142.

The venous signal 138 preserved in the 4D-DSA image 142 illustrates a potential problem when generating 4D images using only a single time-series of 2D images acquired at a single angle. A signal from a desired structure, such as the arterial signal 132, can inadvertently be deposited in 3D voxels representing undesired structures, such as the venous region 138. The unwanted structures thus can be preserved in the 4D image as “shadow artifacts” when their signals lie along the projected values of a desired structure in a dimension inadequately characterized by the time-series of 2D images. This can result, for example, in a 4D-DSA image in which desired arterial structures are obscured by undesired venous structures for some time frames. However, this will cause a temporary anomaly in the contrast vs. time course for the vein. If the time frames of the 4D-DSA image are analyzed, this anomaly can be recognized as inconsistent with the general waveform of the vein, whereby the vein can be suppressed in the time frame where the projected arterial signal is strong. Accordingly, temporal parameters such as mean transit time (MTT) or time-to-fractional-peak can be calculated for each voxel and this information can be used to clean up shadow artifacts. To assist an operator in identifying shadow artifacts and temporal irregularities, the temporal parameters can be color-coded and superimposed on the 4D-DSA image displayed at process block 122. The temporal parameters also can be exploited to infer information related to potential diffusion abnormalities in the absence of direct perfusion information from parenchymal signals.

Referring to FIG. 6, a method for producing 4D-DSA images that are less prone to shadow artifacts begins at process block 144 with the acquisition of image data at a first angle and data acquired at a second angle 146, which is typically separated from the first angle by 60 degrees. This data is preferably acquired as part of the same data set used to form the 3D-DSA volume as illustrated in FIG. 4 but could be acquired from a 2D-DSA image series acquired using a separate injection. At process block 148, the 2D data acquired at the first angle is convolved and multiplied by the 3D-DSA data to form product1. At process block 150, the second angular projection is convolved and multiplied by the 3D-DSA data set to form product2. At process block 152, the square root of the multiplication of product1 and product2 is carried out to form the current 4D-DSA time frame which is displayed at process block 154. At decision block 156, there is a check to see if all frames have been reconstructed. If some of the frames have yet to be processed, the process moves to the next frame at process block 157 and additional frames are reconstructed at process block 146.

As the first angle is advanced, the paired angle is preferably maintained at an angular separation of about 60 degrees. As the first angle increases, the available angular separation of the second and first angle is reduced gradually as the first angle gets within 60 degrees of the final angle acquired in the rotational sweep. Eventually, for the last time frames, the angular separation reduces to zero and the added benefit of the two-angle reduction of shadow artifacts gradually reduces. However, this typically occurs long after the most interesting filing dynamics of the arterial phase have been observed.

Referring now to FIG. 7, when a bi-plane system is used, the angular separation between the projection images used to resolve the shadow artifact can be maintained. The angular projections are preferably obtained with a system in which two source detector pairs are employed to acquire rotational data. In this case, the projections used to embed the time dependence in the 3D rotational data set occur at the same point in time and are always separated by 90 degrees. Alternatively, bi-plane acquisition still can be advantageous if just one source detector pair is used for the 3D rotational acquisition and a separate injection is used to generate orthogonal 2D projections which then can be used to multiply the 3D data set.

In FIG. 7, angular projections are acquired at process block 158. The data acquired for the current time frame at the smallest angle is convolved and multiplied into the 3D data set to form product1 at process block 160. The data acquired for the current time frame at the larger angle is convolved and multiplied into the 3D data set to form product2 at process block 162. At process block 164, the square root of the product of product1 and product2 is formed to generate the current 4D-DSA time frame. This is displayed at processing block 166. At decision block 168 a check to see if all frames have been reconstructed is carried out. If some of the frames have yet to be processed, the process moves to the next frame at process block 169 and additional frames are reconstructed at process block 160. In the bi-plane implementation, the advantages of large angular separation are maintained for all time frames.

FIG. 8 illustrates the use of two angles to remove shadow artifacts. Schematically shown is the formation of a 4D-DSA image frame 220 by selectively combining two registered projection images 222 and 224 and a 3D-DSA image without time dependence 226. Projected arterial signal 228 from the projection images 222 and 224 weights arterial voxels 230 in the 3D-DSA image 226, while the projected signal from pixels without contrast 232 nullifies venous voxels 234 in the 3D-DSA image 226. The resulting 4D-DSA image frame 220, thus, includes weighted arterial signal 236, but does not include undesired venous signals, despite the fact the venous voxels 234 and arterial voxels 230 of the 3D-DSA image are aligned for one of the projection images.

In FIG. 9, this process is illustrated for the case of bi-plane acquisition. The projection of arterial signal 276, that is, pixels having contrast, is indicated generally at 278. The projected values from both of the orthogonal 2D-DSA frames are used to weight the 3D-DSA image and thus produce the 4D-DSA frame 280. Venous signals 284 and 286 are zeroed-out by virtue of being absent in either of the 2D projection images 270 or 274, registered to the 3D-DSA image 272, resulting in the unambiguous isolation of the arterial signal in 282. Again, both the 3D-DSA and orthogonal 2D-DSA images are acquired while a contrast agent is administered to the subject and a signal corresponding to non-vascular structures is removed by subtracting out a mask image.

In some embodiments an alternate approach may be taken reducing shadowing artifacts. As illustrated in FIG. 14, when projections are obtained at different angles, certain projections (as shown, projection 1) may experience vessel overlap, while other projections (as shown, projection 2) are free from vessel overlap. In projection 1, overlap occurs as is indicated for vessels at points A and B. In projection 1 this overlap causes a signal equal to the sum of contributions from A and B. When this projection is multiplied into the time independent 3D volume, each of the vessel signals at A and B are overestimated because of the overlap. In contrast, in projection 2, obtained at a different angle, does not suffer from any overlap of the vessels at A and B. When projection 2 is multiplied into the time independent 3D volume, the correct voxel intensities are obtained for the voxels corresponding to the vessels at points A and B.

Notably, shadowing artifacts of this type will generally always lead to an overestimation of the vessel signal. If the minimum value for the vessel signal obtained at two or more angles is used to represent the vessel at a given voxel, there is a strong likelihood that the correct answer will be obtained provided that there is non-overlap in any of the projections.

Accordingly, the process described above may be modified such that, instead of calculating the vessel signal at a given voxel as the nth root of a product of the multiplication of the 3D volume with the projections at n angles, the vessel signal is calculated by taking the square root of the multiplication of the 3D volume with a single projection at each angle to generate a set of resulting values. The minimum resulting value is chosen as the voxel intensity value for the final image. By repeating on a voxel by voxel basis over all time frames, shadowing artifacts can be reduced or eliminated for each image in the series of time resolved 3D images.

Note that, for the overlap reduction scheme described above, better artifact reduction may be obtained by using a larger number of projection angles for each time frame (thereby increasing the probability that least one projection will be overlap free). However, increasing the number of angles generally causes a tradeoff in reduced temporal resolution. In various embodiments, and suitable number of angles may be used, e.g., at least 2, at least 3, at least 4, at least 5, etc. As described herein, the angles may fall within any suitable range, and may be offset from each other by any suitable value.

As described above, overlap of two different vessels can lead to incorrect estimates of vessel attenuation signals. In the simple case where only one voxel from each vessel is involved, the correct answer may be obtained by taking the minimum value as function of angle.

However, as illustrated in FIG. 15A, anomalous signals can also occur due to overlap of voxels within the same vessels for projection orientations that are directed along the course of the vessel. As shown, four projections, labeled 1, 2, 3, and 4 are taken through a blood vessel. Projections 1, 2, and 4 are oriented transverse to the vessel, and so do not experience self shadowing type overlap. Projection 4, however, runs along the length of a portion of the vessel, leading to self shadowing overlap, resulting in an overestimation of the vessel attenuation signal.

FIG. 15B is a plot of voxel intensity for estimates made at a progression of angles including projections 1 through 4 shown in FIG. 15A. An anomalous perturbation in the signal corresponding to projection 3 can be recognized as a sharp peak in the curve. In any voxel for which this type of effect occurs, the effect can be reduced by time averaging voxel values over multiple projection angles. For example, for the voxel which generates the anomalous curve shown in FIG. 15B, the voxel value can be averaged over the angles for projections 1 through 4. As will be recognized by one skilled in the arts, this corresponds to applying a spatially dependent temporal filter.

For voxels where no anomaly occurs (e.g., where the intensity curve is smooth as a function of projection angle) it can be assumed that no overlap is occurring and the full temporal resolution can be displayed. In regions where significant anomalies in the voxel curve as a function of angle are observed, the values may be smoothed in time by averaging over several angles.

Note that, in some embodiments, anomalies in the voxel intensity curve can be corrected for by interpolation across the anomaly, instead of averaging over multiple angles. Any suitable interpolation algorithm known in the art may be used.

Anomalies in the voxel intensity vs. projection angle curve may be recognized using any suitable technique know in the art. For example, the first derivative of the curve as a function of projection angle may be computed numerically, and anomalies recognized when the rate of change of the intensity as a function of angle exceeds a threshold, exceeds a threshold in the vicinity of a sign change, etc. In other embodiments, peak detection or other curve fitting algorithms may be used to identify anomalies.

Time-resolved 3D images produced in accordance with the present disclosure have significantly improved spatial and temporal resolution in comparison to images produced using traditional methods. Thus time-resolved 3D images produced in accordance with the present disclosure have great utility in the diagnosis, pre-treatment planning, and post-treatment assessment of complex vascular conditions. In addition, these images allow the implementation of time-resolved true 3D roadmaps for use in minimally invasive interventional procedures, thereby facilitating the improved manipulation of surgical devices in complex vasculature. In particular, the present disclosure allows the implementation of 4D fluoroscopy using real-time sequences of surgical device movement combined with spatially and temporally selectable roadmaps obtained from 4D-DSA images. For example, catheter information acquired via either single plane or biplane fluoroscopy can be embedded within 4D-DSA vascular time frames to permit viewing at an arbitrary angle without further gantry movement. Catheter information acquired via real-time single projection subtracted fluoroscopy likewise can be superimposed on 4D-DSA time frames that are registered as the gantry angle is adjusted.

Referring to FIG. 10, in the formation of a fluoroscopic image, it is important that the spatial resolution of the surgical device be maintained. This can differ from the formation of 4D-DSA time frames where time-resolved 2D-DSA time frames are convolved and used to get a local spatial estimate of temporal weighting. It is better to provide an unconvolved and isolated depiction of the surgical device information so that resolution is maintained, though it should be noted that the lack of convolution requires more precise image registration. The formation of images suitable for proper magnification and registration between a moving surgical device, a catheter, and a 4D-DSA image frame is illustrated in FIG. 10. With the catheter mostly out of the field-of-view (FOV), fluoroscopic images 340 and 342 are obtained before and after contrast injection, respectively. These images are subtracted to define an image 344 of the vessel position in the fluoroscopic image series. The catheter is then advanced to obtain image 346, which is subtracted from 340 to form the catheter-only image 348 that is added to a selected 4D-DSA frame 350 to form the 4D fluoroscopic image 352. For comparison, in traditional fluoroscopy, a fluoroscopic image 354 is formed by subtracting the image 346 depicting the advanced catheter from the fluoroscopic image 342 obtained after contrast injection.

When embedding surgical device information acquired via biplane fluoroscopy in 4D-DSA images, the fluoroscopic images are acquired in orthogonal pairs and the above process can be performed for both images. In this case, objects in the resulting 4D fluoroscopic image 352 are registered with the single projection bi-plane images 340-346. Generally, the first step in the registration process is the application of block matching with variable magnification and position in order to register images 344 and 350 in lateral and coronal views. Then the catheter image 348 is added in to form the 4D fluoroscopic image 352, which is registered to the traditional fluoroscopic image 354 using block matching. A range of horizontal and vertical magnifications are typically searched during the registration procedure. For each magnification, a spatially displaced block search can be used to minimize the sum of absolute differences between 4D-DSA time frames and displaced fluoroscopic time frames, and the magnification and translation that minimizes this sum may be chosen for registering the images. To accelerate the search procedure in fluoroscopic dose reduction algorithms, it is possible to employ an iterative block matching technique that initially uses large blocks and then proceeds to smaller blocks.

The formation of a catheter image, such as image 348, can be noisy due to the multiplicative combination of noise from two biplane time-resolved images. Therefore, a noise reduction scheme may be implemented prior to the combination of the catheter image and the 4D-DSA time frame. For example, a spatially adaptive linear filter may be used so that in each element of an image sub-region matrix, the direction of the catheter is determined by calculating the sum of the pixel value within the block as a test object similar in size to the catheter is rotated through the block. The minimal sum is, thus, achieved when the test object has the same orientation as the catheter and a linear convolution filter can be applied along this direction to reduce catheter discontinuities caused by noise in acquired biplane images. Different grid sizes, test object rotation angles, and translation scheduling can be used depending on image quality and processing speed requirements. The size of the linear convolution kernel also can be varied to achieve a desired balance between noise and discontinuity reduction and potential errors in catheter tip localization. Following the application of this spatially adaptive linear filter, a motion adaptive integration of fluoroscopic image frames also can be used to reduce noise. Alternative spatially adaptive filters also may be used to improve the intelligibility of catheter images. For example, another approach is to scan the initial catheter images point-by-point and look at the direction in which the maximum linear sum over some number of pixels occurs. The linear filter then may operate in this direction, since it corresponds to the local orientation of the catheter. Depending on the size of the convolution kernel, the search grid can be adjusted and multiple convolutions of the same catheter segment may be performed.

A distinction should be considered when comparing the relative noise properties of the fluoroscopic and DSA applications. In the case of generating 4D-DSA frames, the anatomical details are supplied by the 3D-image, for example, as acquired by a rotational DSA examination, and the acquisition's individual projections or independently acquired 2D-DSA images provide a local spatially averaged estimate of how much the vasculature is present at each point in time. This spatial average reduces noise and it is not required that the spatial information of the time-dependent frames be maintained. In contrast, it is beneficial to maintain the spatial resolution of the fluoroscopic images depicting the catheter so that there is no intrinsic noise averaging except for that imposed by the filters discussed above. It also should be noted that the computation time for generating 4D-DSA frames and generating 4D fluoroscopic images can differ significantly. It is not necessary to reconstruct 4D-DSA images in real time, whereas fluoroscopic images should be subjected to registration and noise averaging algorithms in real time with minimal latency.

With a biplane fluoroscopy system, surgical device information from an orthogonal time-resolved image series is typically multiplied into a binarized version of the 3D rotational DSA voxels. Following projection from one dimension there is uniform deposition of a surgical device signal across the vasculature depicted in the 3D rotational DSA voxels. The intersection of this signal with a corresponding signal from the orthogonal view carves out the 3D catheter voxels. A single plane system cannot acquire this additional orthogonal view. However, an alternative is to deposit all of the catheter signal in the center of the vessels depicted in a binary rotational DSA display. The maximum intensity projection (MIP) through this data set at any point in time then can be superimposed on the MIP through a corresponding 4D-DSA time frame, thus resulting in images that are roughly equivalent to those produced using biplane methods with the advancement of the surgical device being well represented. This approach of constraining the catheter to the center of a vessel in the direction not captured by the single plane acquisition does not involve any significant disadvantage compared to traditional fluoroscopic views in which catheter position is unknown in one direction.

For systems without biplane capabilities, the flexibility of roadmap selection provided by the 4D-DSA time frames additionally can be exploited by superimposing the single plane fluoroscopy on the MIP of the 4D-DSA time frame taken at a given gantry angle. This involves registration at just the current projection for each gantry angle. Because it is not necessary that orthogonal surgical device views intersect to form a 3D spatial catheter volume, registration is of less importance and the full image quality of live fluoroscopy is essentially maintained. It is contemplated that this gantry rotation mode offers improved SNR, since it does not involve the multiplicative noise effects that occur when embedding biplane surgical device information into a 4D-DSA image, as discussed above, to establish a 4D fluoroscopic volume without gantry rotation.

For fluoroscopic applications in which there are likely to be multiple positions of the interventional device within the vascular lumen, ambiguous intersections of current information and information associated with the past history of the device trajectory can arise. Because of this, the fluoroscopic image series generated at 352 in FIG. 10 are sequentially subtracted using a frame separation of at least one in order to isolate the most recent change in device position. The differential signals in the biplane views are well-correlated in time and, when multiplied by the 3D data set, reliably isolate the current position of the tip of the device. This is illustrated in FIG. 11 where the current device tip is shown at times t1-t4. A display of the device path is formed by summing the past catheter position signals using a simple sum or a recursive filter. This display can be reset by the operator to reinitiate integration.

FIG. 12 illustrates the method for employing partial angle filtered back projection (FBP) images to weight the information in the 3D-DAS volume to form 4D-DSA time frames. Partial angle sector data are acquired as a function of time as shown in 356 and 358. The angular sectors are advanced as time goes on. For a single plane system, a single sector of projection angles is acquired for each time frame. For a system employing two source detector sets, the number of sectors is increased to two resulting in an improved reconstruction. In a flowchart 360 of the method, the FBP image is formed at process block 362 and used to weight the 3D volume data at process block 364 to form a 4D-DSA time frame that is displayed at process block 366. At decision block 368, a decision is made regarding the need to reconstruct new frames in which case the process returns to 362.

When it is desired to generate time-dependent 3D volumes depicting tissue perfusion it is desirable to remove vascular information from the weighting image. This can be done by applying a threshold eliminating signal above a user-defined level. This step can be incorporated into an “expanded” processing step 362 prior to weighting the 3D volume in processing block 364 as shown in FIG. 13. This process diminishes the effects of errors in the reconstruction of the vessels that might compete with the tissue perfusion signals.

One or more or any part thereof of the techniques described herein can be implemented in computer hardware or software, or a combination of both. The methods can be implemented in computer programs using standard programming techniques following the method and figures described herein. Program code is applied to input data to perform the functions described herein and generate output information. The output information is applied to one or more output devices such as a display monitor. Each program may be implemented in a high level procedural or object oriented programming language to communicate with a computer system. However, the programs can be implemented in assembly or machine language, if desired. In any case, the language can be a compiled or interpreted language. Moreover, the program can run on dedicated integrated circuits preprogrammed for that purpose.

Each such computer program is preferably stored on a storage medium or device (e.g., ROM or magnetic diskette) readable by a general or special purpose programmable computer, for configuring and operating the computer when the storage media or device is read by the computer to perform the procedures described herein. The computer program can also reside in cache or main memory during program execution. The analysis, preprocessing, and other methods described herein can also be implemented as a computer-readable storage medium, configured with a computer program, where the storage medium so configured causes a computer to operate in a specific and predefined manner to perform the functions described herein. In some embodiments, the computer readable media is tangible and substantially non-transitory in nature, e.g., such that the recorded information is recorded in a form other than solely as a propagating signal.

It is to be understood that any of the signals and signal processing techniques may be digital or analog in nature, or combinations thereof.

The present disclosure is not to be limited in terms of the particular embodiments described in this application. Many modifications and variations can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the disclosure, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the appended claims. The present disclosure is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled. It is to be understood that this disclosure is not limited to particular methods components, implementations, etc. which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc.

As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 particles refers to groups having 1, 2, or 3 particles. Similarly, a group having 1-5 particles refers to groups having 1, 2, 3, 4, or 5 particles, and so forth.

While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.

All references cited herein are incorporated by reference in their entireties and for all purposes to the same extent as if each individual publication, patent, or patent application was specifically and individually incorporated by reference in its entirety for all purposes.

Although the present disclosure has been described with reference to specific embodiments, those of skill in the art will recognize that changes may be made thereto without departing from the spirit and scope of the present disclosure as set forth in the hereafter appended claims. 

What is claimed is:
 1. A method for producing a time-resolved three-dimensional image of a subject, the method comprising: acquiring image projection data from the subject using a medical imaging system during a single contrast injection, the medical imaging system including a single source/single detector system; generating a time-series of two-dimensional images from at least a portion of the acquired image projection data; reconstructing a three-dimensional image substantially without temporal resolution from at least a portion of the acquired image projection data; and producing a time-resolved three-dimensional image having a signal-to-noise ratio substantially higher than a signal-noise-ratio of the acquired image projection data by selectively combining the three-dimensional image substantially without temporal resolution and the time-series of two-dimensional images; wherein a subtracted vessel-only time-series of two-dimensional images is generated by subtracting at least one of a time frame of the time-series and an average of time frames of the time-series acquired before arrival of contrast from frames of the time-series acquired after an arrival of contrast during the single contrast injection; and further comprising: registering the reconstructed three-dimensional image substantially without temporal resolution to the subtracted vessel-only time-series of two-dimensional images; convolving the subtracted vessel-only time-series of two-dimensional images using a two-dimensional spatial kernel; projecting a value of each pixel in the subtracted vessel-only time-series of two-dimensional images along a line extending through each respective pixel in a direction perpendicular to a plane of the time-series of two-dimensional images; and multiplying the three-dimensional image substantially without temporal resolution with the projected value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images to produce the time-resolved three-dimensional image; wherein a signal in the time-resolved three-dimensional image corresponding to undesired vascular structures in a region being imaged is zeroed by multiplication of the three-dimensional image substantially without temporal resolution with the projected value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images, which is substantially free of signals corresponding to undesired vascular structures in the region being imaged; wherein multiplying the three-dimensional image is repeated at additional angles; wherein: i) the final image is derived from the minimum values resulting from image estimates obtained by multiplication at two or more angles; or ii) the method further comprises: calculating one or more voxel intensity curves as a function of multiple projection angles for the time resolved three dimensional image; identifying at least one anomaly in at least one voxel intensity curve; and for the voxel corresponding to the anomaly, averaging the voxel intensity over multiple projection angles.
 2. A method as claimed in claim 1, wherein: the final image is derived from the minimum values resulting from image estimates obtained by multiplication at two or more angles;
 3. A method as claimed in claim 2, wherein for each time frame, the minimum values are determined on a voxel by voxel basis.
 4. A method as claimed in claim 3, wherein, for each time frame, each of the image estimates obtained by multiplication at two or more angles comprises a square root of the product of the three-dimensional image substantially without temporal resolution with a projection at a respective one of the two or more angles.
 5. A method as claimed in claim 5, wherein the method further comprises: calculating one or more voxel intensity curves as a function of multiple projection angles for the time resolved three dimensional image; identifying at least one anomaly in at least one voxel intensity curve; and for the voxel corresponding to the anomaly, averaging the voxel intensity over multiple projection angles.
 6. The method as claimed in claim 5, comprising applying a spatially dependent temporal filter to the time resolved three dimensional image.
 7. A method as claimed in claim 1, further comprising determining a temporal parameter for each voxel of the time-resolved three-dimensional image, wherein the temporal parameter is at least one of a mean transit time and time-to-fractional peak.
 8. A method as claimed in 7, wherein determining a temporal parameter includes removing shadowing artifacts from the time-resolved three-dimensional image based on the temporal parameter.
 9. A method as claimed in claim 7, wherein determining a temporal parameter includes superimposing a color coded display of the temporal parameter on at least one of the time-resolved three-dimensional image and a blood volume image generated from the three-dimensional image substantially without temporal resolution.
 10. A method as claimed in claim 1, wherein the image projection data are acquired at a fixed position of a source detector gantry of the single source/single detector system until injected contrast is detected in a field of view and generates adequate arterial and venous contrast to permit acquisition of a three-dimensional rotational data set with substantially uniform contrast throughout whereby rotation of the source detector gantry is initiated.
 11. A method as claimed in claim 10, wherein additional time-resolved outflow projection data are acquired at a final angle of the three-dimensional rotational data set acquisition and are used to produce three-dimensional time resolved outflow volumes.
 12. A method as claimed in claim 1, wherein the single contrast injection is one of an intra-arterial injection and an intra-venous injection.
 13. A method for producing a time-resolved three-dimensional image of a subject, the method comprising: acquiring image projection data from the subject using a medical imaging system during multiple contrast injections acquired at multiple source-detector orientations, the medical imaging system including a single source/single detector array; and generating a subtracted vessel-only time-series of two-dimensional images from the acquired image projection data at the multiple source-detector orientations; wherein the image projection data is acquired at multiple rotation angles during one of the multiple contrast injections; wherein a three-dimensional image substantially without temporal resolution is reconstructed from at least a portion of the acquired image projection data; further comprising: producing a time-resolved three-dimensional image with a signal-to-noise ratio substantially higher than a signal-to-noise ratio of the acquired image projection data by selectively combining the three-dimensional image substantially without temporal resolution and the subtracted vessel-only time-series of two-dimensional images; wherein a signal in the time-resolved three-dimensional image corresponding to undesired vascular structures in a region being imaged is zeroed by multiplication of the three-dimensional image substantially without temporal resolution with the projected value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images, which is substantially free of signals corresponding to undesired vascular structures in the region being imaged; wherein multiplying the three-dimensional image is repeated at additional angles; and wherein: i) the final image is derived from the minimum values resulting from image estimates obtained by multiplication at two or more angles; or ii) the method further comprises: calculating one or more voxel intensity curves as a function of multiple projection angles for the time resolved three dimensional image; identifying at least one anomaly in at least one voxel intensity curve; and for the voxel corresponding to the anomaly, averaging the voxel intensity over multiple projection angles.
 14. A method as claimed in claim 13, wherein the final image is derived from the minimum values resulting from image estimates obtained by multiplication at two or more angles.
 15. A method as claimed in claim 14, wherein, for each time frame, the minimum values are determined on a voxel by voxel basis.
 16. A method as claimed in claim 15, wherein, for each time frame, each of the image estimates obtained by multiplication at two or more angles comprises a square root of the product of the three-dimensional image substantially without temporal resolution with a projection at a respective one of the two or more angles.
 17. A method as claimed in claim 13, the method further comprising: calculating one or more voxel intensity curves as a function of multiple projection angles for the time resolved three dimensional image; identifying at least one anomaly in at least one voxel intensity curve; and for the voxel corresponding to the anomaly, averaging the voxel intensity over multiple projection angles.
 18. A method as claimed in claim 17, comprising applying a spatially dependent temporal filter to the time resolved three dimensional image.
 19. A method as claimed in claim 13, further comprising determining a temporal parameter for each voxel of the time-resolved three-dimensional image, wherein the temporal parameter is at least one of a mean transit time and time-to-fractional peak.
 20. A method as claimed in claim 13, wherein determining a temporal parameter includes removing shadowing artifacts from the time-resolved three-dimensional image based on the temporal parameter.
 21. A method as claimed in claim 20, wherein determining a temporal parameter includes superimposing a color coded display of the temporal parameter on at least one of the time-resolved three-dimensional image and a blood volume image generated from the three-dimensional image substantially without temporal resolution.
 22. A method as claimed in claim 13, wherein the multiple contrast injections are one of intra-arterial injections and intra-venous injections.
 23. A method for producing a time-resolved three-dimensional image of a subject, the method comprising: acquiring image projection data from the subject using a medical imaging system during a single contrast injection, the medical imaging system including a bi-plane system having two separate source detector systems; generating a subtracted vessel-only time-series of two-dimensional images from at least a portion of the acquired image projection data from each of the source detector systems obtained at multiple angles; reconstructing a three-dimensional image substantially without temporal resolution from at least a portion of the acquired image projection data; producing a time-resolved three-dimensional image having a signal-to-noise ratio substantially higher than a signal-to-noise ratio of the acquired image projection data by selectively combining the three-dimensional image substantially without temporal resolution and the subtracted vessel-only time-series of two-dimensional images; registering the reconstructed three-dimensional image substantially without temporal resolution to the subtracted vessel-only time-series of two-dimensional images obtained at multiple angles; convolving the subtracted vessel-only time series of two-dimensional images using a two-dimensional spatial kernel; projecting a value of each pixel in the subtracted vessel-only time-series of two-dimensional images along a line extending through each respective pixel in a direction perpendicular to a plane of the subtracted vessel-only time-series of two-dimensional images; and multiplying the three-dimensional image substantially without temporal resolution with the value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images to produce the time-resolved three-dimensional image; wherein a signal in the time-resolved three-dimensional image corresponding to undesired vascular structures in a region being imaged is zeroed by multiplication of the three-dimensional image substantially without temporal resolution with the projected value of each pixel for each time frame of the subtracted vessel-only time-series of two-dimensional images, which is substantially free of signals corresponding to undesired vascular structures in the region being imaged; and wherein: i) the final image is derived from the minimum values resulting from image estimates obtained by multiplication at two or more angles; or ii) the method further comprises: calculating one or more voxel intensity curves as a function of multiple projection angles for the time resolved three dimensional image; identifying at least one anomaly in at least one voxel intensity curve; and for the voxel corresponding to the anomaly, averaging the voxel intensity over multiple projection angles.
 24. A method as claimed in claim 23, wherein the final image is derived from the minimum values resulting from image estimates obtained by multiplication at two or more angles.
 25. A method as claimed in claim 24, wherein, for each time frame, the minimum values are determined on a voxel by voxel basis.
 26. A method as claimed in claim 25, wherein, for each time frame, each of the image estimates obtained by multiplication at two or more angles comprises a square root of the product of the three-dimensional image substantially without temporal resolution with a projection at a respective one of the two or more angles.
 27. A method as claimed in claim 23, the method further comprising: calculating one or more voxel intensity curves as a function of multiple projection angles for the time resolved three dimensional image; identifying at least one anomaly in at least one voxel intensity curve; and for the voxel corresponding to the anomaly, averaging the voxel intensity over multiple projection angles.
 28. The method as claimed in claim 27, comprising applying a spatially dependent temporal filter to the time resolved three dimensional image.
 29. A method as claimed in claim 23, further comprising determining a temporal parameter for each voxel of the time-resolved three-dimensional image, wherein the temporal parameter is at least one of a mean transit time and time-to-fractional peak.
 30. A method as claimed in claim 29, wherein determining a temporal parameter includes removing shadowing artifacts from the time-resolved three-dimensional image based on the temporal parameter.
 31. A method as claimed in claim 30, wherein determining a temporal parameter includes superimposing a color coded display of the temporal parameter on at least one of the time-resolved three-dimensional image and a blood volume image generated from the three-dimensional image substantially without temporal resolution.
 32. A method as claimed in claim 23, wherein the image projection data are acquired at fixed positions of two source detector gantries of the respective two source detector systems until injected contrast is detected in a field of view and generates adequate arterial and venous contrast to permit acquisition of a 3D rotational data set with substantially uniform contrast throughout whereby rotation of at least one of the two source detector gantries is initiated.
 33. A method as claimed in claim 32, wherein additional time-resolved outflow projection data are acquired at a final angle of the three-dimensional rotational data set acquisition and are used to produce three-dimensional time resolved outflow volumes. 